Growth Retardation, Duodenal Lesions, and Aberrant Ileum Architecture in Triple Null Mice Lacking EGF, Amphiregulin, and TGF-α

Troyer, Kelly L.; Luetteke, Noreen; Saxon, Marian L.; Qiu, Ting; Chen, Xian; Lee, Dong Hoon

doi:10.1053/gast.2001.25478

Cited by 94 publications

(71 citation statements)

References 37 publications

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“…Mice lacking EGF, TGF-α or amphiregulin fail to recapitulate the full range of EGFR-knockout phenotypes. EGF-and amphiregulin-null mice do not have an easily identifiable phenotype [131,132]. Targeted and naturally occurring (waved-1) mutations of TGF-α in mice leads to defects in hair follicle and eye development, phenotypes similar to the spontaneous EGFR mutation of the waved-2 mouse [133][134][135].…”

Section: Erbb Members In Mammalian Developmentmentioning

confidence: 99%

“…Female mice with combined deficiency of amphiregulin, EGF and TGF-α display diminished mammary gland ductal outgrowth during puberty with severe defects in mammopoeisis and lactogenesis [131]. Triple mutant mice deficient in EGF, TGF-α, and amphiregulin partially phenocopy EGFR-deficient mice, displaying decreased cell proliferation in the intestine leading to attenuated ileal villi and decreased mucin production [132].…”

Section: Erbb Members In Mammalian Developmentmentioning

confidence: 99%

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The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

647

503

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The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.

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Section: Erbb Members In Mammalian Developmentmentioning

confidence: 99%

Section: Erbb Members In Mammalian Developmentmentioning

confidence: 99%

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

647

503

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“…EGFR can be activated by several ligands, including epidermal growth factor (EGF), transforming growth factor (TGF)-α, heparin-binding EGF (HBEGF), betacellulin (Btc), amphiregulin (AREG), and epiregulin (EREG). Although mice lacking TGF-α, EGF, or AREG individually do not show any gastrointestinal phenotype, triple null mice lacking EGF, AREG, and TGF-α show duodenal lesions and aberrant ileum architecture (16). Moreover, mice lacking TGF-α or EREG or EGFR kinase-defective Waved-2 mice are highly susceptible to chemically induced colitis using DSS (14,15,17).…”

mentioning

confidence: 99%

MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands

Brandl

Sun

Neppl

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

134

129

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Toll-like receptors (TLRs) trigger intestinal inflammation when the epithelial barrier is breached by physical trauma or pathogenic microbes. Although it has been shown that TLR-mediated signals are ultimately protective in models of acute intestinal inflammation [such as dextran sulfate sodium (DSS)-induced colitis], it is less clear which cells mediate protection. Here we demonstrate that TLR signaling in the nonhematopoietic compartment confers protection in acute DSS-induced colitis. Epithelial cells of MyD88/Trif-deficient mice express diminished levels of the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG), and systemic lipopolysaccharide administration induces their expression in the colon. N -ethyl- N -nitrosourea (ENU)-induced mutations in Adam17 (which is required for AREG and EREG processing) and in Egfr both produce a strong DSS colitis phenotype, and the Adam17 mutation exerts its deleterious effect in the nonhematopoietic compartment. The effect of abrogation of TLR signaling is mitigated by systemic administration of AREG. A TLR→MyD88→AREG/EREG→EGFR signaling pathway is represented in nonhematopoietic cells of the intestinal tract, responds to microbial stimuli once barriers are breached, and mediates protection against DSS-induced colitis.

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“…Gene targeting experiments have demonstrated that mice null for EGF, AR (Luetteke et al, 1999), or TGF-alpha (Mann et al, 1993) are fertile. In addition, compound knockouts for all three alleles are still fertile (Troyer et al, 2001).…”

Section: Epidermal Growth Factormentioning

confidence: 99%

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Klein¹,

Bauersachs²,

Ulbrich³

et al. 2006

Reprod. Fertil. Dev.

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Early embryonic development, implantation, and maintenance of a pregnancy are critically dependent on an intact embryo-maternal communication. So far, only few signals involved in this dialogue have been identified. In ruminants, interferon tau (IFN�) plays a key role in the process of maternal recognition of pregnancy by exhibiting antiluteolytic activity. Even though many experimental findings indicate a pivotal role of IFN� in the context of embryo-maternal communication in ruminants, a number of other systems may be involved. To identify genes induced in the bovine endometrium by the signaling of the embryo, a combination of subtracted cDNA libraries and cDNA array hybridization was applied. Monozygotic twin pairs (n = 5) were used as the biological model. Pregnancy was created in one twin by transferring two in vitro-produced embryos on Day 7 of the estrous cycle; the other twin received a sham embryo transfer. Pregnant and nonpregnant twins were slaughtered at Day 18; endometrial tissue samples were recovered and processed for transcriptome analysis as described (Bauersachs et al. 2005 J. Mol. Endocrinol. 34, 889-908). Screening of 4608 clones of two subtracted libraries revealed 90 different up-regulated genes and mRNAs, of which almost 50% are known to be stimulated by type I interferons. Among these interferon-stimulated genes, the ISG15 system is assumed to be of particular interest, and several components were studied in more detail using in situ hybridization. The pattern of mRNA expression suggests that modification of endometrial proteins through ISG15ylation plays a fundamental role during the pre-implantation period. A classification of the identified genes based on Gene Ontologies revealed the prevalence of genes involved in regulation of gene expression, cell communication, cell growth, cell differentiation, cell proliferation, and cell adhesion, and also the prevalence of genes with immune-related functions. These results underline the intense response of the endometrium to the presence of a conceptus, culminating in the preparation of the maternal environment for embryonic implantation. Further, for eleven selected genes the expression in the endometrium was quantified by the use of real-time RT-PCR. Overall, the results of quantitative RT-PCR and array hybridization correlated very well. To our knowledge this study provides the first holistic gene expression analysis of the bovine endometrium during the pre-implantation period. The results underline the importance of IFN� as an embryo-derived pregnancy recognition signal and depict the molecular mechanisms at the mRNA level underlying the intense embryo-maternal dialog taking place at Day 18 of gestation.

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Growth Retardation, Duodenal Lesions, and Aberrant Ileum Architecture in Triple Null Mice Lacking EGF, Amphiregulin, and TGF-α

Abstract: EGF-R ligands are required for development and mucosal maintenance in mouse small intestine. Both maternal and neonatal sources of growth factors are required for optimal pup growth.

Cited by 94 publications

References 37 publications

The epidermal growth factor receptor family: Biology driving targeted therapeutics

The epidermal growth factor receptor family: Biology driving targeted therapeutics

MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

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